Download Transmission of hepatitis B, hepatitis C and human

Transmission of hepatitis B, hepatitis C and
human immunodeficiency viruses through
unsafe injections in the developing world:
model-based regional estimates
A. Kane,1 J. Lloyd,2 M. Zaffran,3 L. Simonsen,4 & M. Kane5
Thousands of millions of injections are delivered every year in developing countries, many of them unsafe, and the
transmission of certain bloodborne pathogens via this route is thought to be a major public health problem. In this
article we report global and regional estimates of the number of hepatitis B virus (HBV), hepatitis C virus (HCV) and
human immunodeficiency virus (HIV) infections that may occur from unsafe injections in the developing world. The
estimates were determined using quantitative data on unsafe injection practices, transmission efficiency and disease
burden of HBV, HCV and HIV and the prevalence of injection use obtained from a review of the literature.
A simple mass-action model was used consisting of a generalized linear equation with variables accounting for
the prevalence of a pathogen in a population, susceptibility of a population, transmission efficiency of the pathogen,
proportion of injections that are unsafe, and the number of injections received. The model was applied to world census
data to generate conservative estimates of incidence of transmission of bloodborne pathogens that may be
attributable to unsafe injections. The model suggests that approximately 8±16 million HBV, 2.3±4.7 million HCV and
80 000±160 000 HIV infections may result every year from unsafe injections. The estimated range for HBV infections is
in accordance with several epidemiological studies that attributed at least 20% of all new HBV infections to unsafe
injections in developing countries. Our results suggest that unsafe injections may lead to a high number of infections
with bloodborne pathogens. A major initiative is therefore needed to improve injection safety and decrease injection
overuse in many countries.
Keywords: hepatitis B; hepatitis C; HIV infections, injections; linear models; risk factors.
Voir page 806 le reÂsume en francËais. En la paÂgina 806 figura un resumen en espanÄol.
Introduction
Transmission of bloodborne pathogens through
contaminated needles and syringes has long been
recognized (1). However, the extent of this problem
in developing countries has been poorly quantified.
Increased rates of bloodborne infections in exposed
groups, such as health care workers and injecting
drug users, have been well described in the
industrialized world (2±5). This has resulted in
routine immunization against viral hepatitis B and
measures to prevent needle-stick injuries in health
care workers (6). Before widespread hepatitis B
1
Trinity College, Duke University, Durham, NC, USA.
2
Technical Officer, Department of Vaccines and Other Biologicals,
World Health Organization, Geneva, Switzerland.
3
Programme Officer, Department of Vaccines and Other Biologicals,
World Health Organization, 1211 Geneva 27, Switzerland. Correspondence should be addressed to this author. E-mail: [email protected]
4
Medical Officer, Department of Communicable Disease Surveillance
and Response, World Health Organization, Geneva, Switzerland.
5
Director, Bill and Melinda Gates Children's Vaccines Program,
Program for Appropriate Technology in Health, Seattle, USA.
Ref. No. 0050
Bulletin of the World Health Organization, 1999, 77 (10)
immunization, it was estimated that approximately
8700 cases of viral hepatitis B from percutaneous
exposures, mostly needle-sticks, occurred every year
in the USA (7). Supplies of free needles and bleach
disinfection kits have been distributed in many cities
to control disease transmission among injecting drug
users (8, 9). However, the transmission of disease to
health care workers and between injecting drug users
in industrialized countries is only a small fraction of
the total transmission from contaminated needles
and syringes worldwide.
Thousands of millions of injections, many of
them unsafe, are given each year in developing
countries. WHO defines a safe injection as one that
does not harm the recipient, the health care worker or
the community. For the purpose of this paper, we
defined an unsafe injection as reuse of a syringe or
needle from patient to patient without sterilization.
The high prevalence of bloodborne pathogens, the
popularity and overuse of injections, and the high
proportion of injections that are unsafe have
generated concern (10±13). Although the spread of
human immunodeficiency virus (HIV) among injecting drug users has been modelled (8), no global
estimates for nosocomial patient-to-patient transmis#
World Health Organization 1999
801
In Focus
sion of hepatitis B virus (HBV), hepatitis C virus
(HCV) and HIV have been published.
We have developed a simple modelling approach that permits quantification of the risk of
cross-infection due to unsafe injections, and which
considers variables such as susceptibility of the
patient, transmission efficiency of a virus, prevalence
of a virus, proportion of injections that are unsafe and
number of injections received. The model is similar
to that used by Aylward (14) and Allard (15).
Elsewhere in this issue we have reviewed and
compiled from the literature all available data on
quantitative aspects of unsafe injection practices in
developing countries (16) and estimated the proportion of injections that may be unsafe. The number of
injections received per capita per year was also
estimated, based on Expanded Programme on
Immunization (EPI) country reports, as well as data
in the published literature. For this study, we used
median parameter values from the review (16) to
generate an estimate of the number of HBV, HCV
and HIV infections that occur from unsafe injections
in various geographical regions in the developing
world.
Method
The model approach
We created a model consisting of a simple generalized
linear equation for calculating the probability that an
average individual in a particular geographical region
will acquire the infectious agent of interest each year.
This probability was then multiplied by population
size for each world region to give an estimate of the
incidence of transmission of bloodborne pathogens
per year.
The equation used to estimate the individual
risk of becoming infected is as follows:
P(I) = 1 ± (1 ± P(s). P(t). P(e))n,
where P(I) is the probability of an individual
becoming infected each year, P(s) is the probability
that the individual is susceptible to the organism, P(t)
is the probability that the organism will be transmitted given the injection equipment is contaminated
with infectious blood, P(e) is the probability that the
individual is exposed to injection equipment contaminated with infectious blood, and n is the number
of injections that an individual receives in a one-year
period.
P(e) is a function of the prevalence of an
organism, P(v), and the proportion of injections that
are unsafe, P(u). P(e) was calculated using the
following equation:
P(e) = P(v). P(u).
Susceptibility to HBV is a function of the
prevalence of active infection with hepatitis B surface
antigen (HBsAg) and the prevalence of immunity,
defined as possession of surface antibody (anti-HBs)
such that:
802
P(s) = 1 ± [Prevalence(HBsAg-positive) +
Prevalence(anti-HBs-positive)]
For modelling HCV and HIV transmission, we
assumed that susceptibility was a function of the
prevalence of HIV and HCV in the particular
population, such that for HIV:
P(s) = 1 ± Prevalence(HIV-positive individuals).
The following assumptions are implicit in this
model:
± everyone in a population (i.e. sick and not sick)
receives the same number of injections;
± all members of a population are equally at risk of
becoming infected from an unsafe injection.
Results
Parameter values
For the model, the variables that have been well
documented in the literature include the prevalence
and transmissibility of particular diseases, and the
probability that an individual, in a specific population
or population subgroup, would be susceptible to the
pathogen. The variables that have not previously
been established in the literature, and which were
therefore estimated for the model, include the
proportion of injections that are unsafe and the
number of injections received.
The parameters used for modelling were
median values generated from the data compiled
and analysed in our literature review (16).
The transmission efficiency, P(t), of an infectious agent was assumed to be the same as for
needle-stick injuries in health care workers. Median
values of P(t) were 0.3% for HIV, 30% for hepatitis B
carriers, and 6% for HCV carriers (16). The hepatitis
B transmission was taken to be 30% because many
infected people are e-antigen-positive in the developing world. The actual transmissibility of these
organisms through an unsafe medical injection may
be higher than for a needle-stick injury owing to
possible contamination of the syringe, although the
quantity of blood found at needle-stick and injection
sites has been found to be similar (17).
Prevalence of injections
Approximately 25 billion (25 thousand million)
syringes are used globally each year, at least half of
them for injections (Becton Dickinson, personal
communication, 1999). This number is consistent
with EPI country reports, that about a thousand
million injections per year are given for immunization
purposes, and that 8±12 curative injections are given
for each immunization injection (18). Thus, we assume
that 8±12 billion injections are given worldwide each
year in the health sector, roughly 1.5±2 injections per
person per year. The literature review (16) reports an
average incidence of 1.5 injections per person per year,
with a range of 0.9±7.5. Therefore, for the purposes of
Bulletin of the World Health Organization, 1999, 77 (10)
Transmission of HBV, HCV, and HIV through unsafe injections
the model, we allowed the number of yearly injections
per person (n) to range from 1 to 2.
Prevalence of bloodborne pathogens
The prevalences of HIV, HBV and HCV infections
by world region are presented in Table 1 (19±21).
Prevalence of unsafe injections
The most critical variable is the proportion of
injections that are unsafe, P(u). From the quantitative
data reviewed (16), estimates for P(u) were made
(Table 2).
The WHO regional classifications do not
distinguish industrialized versus developing countries. Therefore, for the model, countries were
grouped by the standard World Bank regional
classifications, as follows:
± Established market economies;
± Latin America and the Caribbean;
± Sub-Saharan Africa;
± Former Socialist Economies of Europe
± India;
± China;
± Middle Eastern crescent;
± Other Asian and Pacific islands.
At least 50% of injections were unsafe in 14 of
19 countries (representing five world regions) for
which data were available. Since the precise proportion of injections that are unsafe is not known, and as
this parameter is the most controversial, we chose
for the model the median value (50%) for regions in
Asia and sub-Saharan Africa. The lowest levels of
safety were assumed to occur in sub-Saharan Africa
and in Asia, where at least 50% of injections were
unsafe in all but three countries for which data were
available (16). For the Middle Eastern crescent and
the former socialist economies of Europe, the
proportion of injections that are unsafe has not
been addressed in many studies, but is assumed to be
lower than in Africa or Asia. In two wealthy
countries in the Middle Eastern crescent, injection
safety was reported to be excellent, but in other
countries, such as Pakistan, more than 80% of
injections were unsafe (16). Because economic
diversity and quality of health services are highly
variable, we conservatively estimated that a median
of 15% of injections were unsafe in these regions.
For Latin America, data on unsafe injection practices
were only available for one small country, and
therefore model-based estimates of viral transmission in this region were not made.
Model results
According to our model (Table 2), the highest
numbers of infections from unsafe injections occur
in Asia and sub-Saharan Africa, where the prevalence
of the pathogens is highest and injection safety
poorest. The model calculates that approximately
8±16 million HBV, 2.3±4.7 million HCV and 80 000±
160 000 HIV infections may occur annually due to
Bulletin of the World Health Organization, 1999, 77 (10)
Table 1. Population and prevalence of hepatitis B carriers, hepatitis
C virus (HCV), and human immunodeficiency virus (HIV), by region
Region
Established market
economies
Latin America and
the Caribbean
Former Socialist
Economies of Europe
Middle Eastern crescent
India
China
Sub-Saharan Africa
Other Asian countries
and Pacific islands
Population Hepatitis
HCV
HIV
(x 1000) B carriers prevalence prevalencea
669 606
0.005
0.020
0
456 963
0.001
0.020
0.00340
413 443
0.040
0.020
0.04000
481 752
871 158
1 155 795
520 425
837 373
0.040
0.040
0.120
0.100
0.100
0.020
0.019
0.041
0.020
0.020
0.00034
0.00200
0.00010
0.04100
0.00620
a
HIV prevalence for the total population. Note: these prevalence rates differ from figures
provided by UNAIDS, where prevalence rates are based on the sexually active population only
(i.e. those aged 15±49 years).
unsafe injections. The ranges were generated considering that between 1 and 2 injections are received
per person per year on average.
If a sterile needle and syringe are used for each
injection, the number of resulting infections is zero.
As the sensitivity analyses demonstrate (Fig.1), for
many realistic parameter values an essentially linear
relationship exists between the proportion of injections that are unsafe and the number of HIV, HBV
and HCV infections that could occur. Thus, reducing
the proportion of injections that are unsafe by one
half reduces the number of infections by one half.
The HIV estimates demonstrate that, for a disease
with a relatively low transmissibility and prevalence,
unsafe injections can result in substantial transmission in situations where susceptibility is high.
Discussion
Unsafe injections are a major public health problem in
many areas of the developing world for the following
reasons: the high prevalence of certain bloodborne
diseases (1); the enormous popularity and overuse of
injectable therapy (10); and the high proportion of
these injections that are unsafe (16). Considering that
8±12 billion injections are given yearly, and that 50%
of these are unsafe in most of the countries in the
developing world, we estimate, using a simple linear
mass-action model, that this situation results in
approximately 8±16 million HBV infections, 2.3±4.7
million HCV infections and 80 000±160 000 HIV
infections per year. Enormous numbers of additional
injections are given outside the health sector, in
markets, by traditional and unlicensed practitioners,
with the ``family syringe'', and by dentists. Other
parenteral exposures, such as scarification, skinpiercing, circumcision, tattooing and acupuncture also
carry high risk of transmission of bloodborne
pathogens, and are not included in these estimates.
803
In Focus
Table 2. Estimated proportion of unsafe injections and estimated number of hepatitis B (HBV), hepatitis
C (HCV), and human immunodeficiency virus (HIV) infections, by region
Region
Established market
economies
Latin America and
the Caribbean
Former Socialist
Economies of Europe
Middle Eastern crescent
India
China
Sub-Saharan Africa
Other Asian countries
and Pacific islands
Total
a
Proportion
of unsafe
injections,
P (u)
n=1
HBV
n=2
n=1
HIV
n=2
0
0
0
0
0
0
0
NA
NA
NA
NA
NA
NA
NA
0.15
446 278
892 555
60 772
121 543
11 907
23 814
0.15
0.50
0.50
0.50
0.50
520 011
3 130 524
2 078 559
780 052
1 255 118
1 040 022
6 261 047
4 157 117
1 560 104
2 510 235
70 813
405 430
1 136 743
254 946
410 212
141 625
810 859
2 273 485
509 892
820 424
122
4 312
286
51 208
12 850
243
8 624
572
102 415
25 699
8 210 541
16 421 081
2 338 915
4 677 829
80 684
161 367
n = No. of injections received per person per year; NA = not available.
As part of a new injection safety initiative at
WHO, we have performed a literature review
gathering quantifiable data from all available studies
on unsafe injection practices, popularity of injections,
and studies linking unsafe injections to transmission
of bloodborne pathogens (16). Unfortunately, the
status of injection safety has been addressed by
relatively few studies, and many countries are poorly
represented or simply lacking in any appropriate data
at all. The accuracy of our estimates depends on how
generalizable the available data are, and how our
simple mass-action model would compare with more
complex, stratified models. Our model estimates for
hepatitis B transmission via unsafe injections were in
agreement with several epidemiological studies that
attributed at least 20% of new hepatitis B infections
to unsafe injections (16). WHO estimates that
approximately 67 million new hepatitis B infections
occur yearly (22). The global contribution of unsafe
injections to the transmission of HCV and HIV
remains unclear. In certain cases, however, the
essential contribution of unsafe injections has been
clearly demonstrated for outbreaks of these diseases,
most notably the HIV outbreak in orphanages in
Romania (23), and HCV transmission in Egypt
(24, 25).
Previous models of cross-infection risk (14, 15)
took into account the possibility that contaminated
injection equipment could place more than just the
next susceptible recipient at risk. These models
included an additional variable, which allowed either
variance in the number of times a needle is reused
(14), or in the number of subsequent susceptible
recipients at risk of infection once equipment has
been contaminated (15). The authors stressed that
there is a nonlinear relationship between the number
of infections in a population and the number of times
804
Estimated no. of infectionsa
HCV
n=1
n=2
a needle is reused. The risk to a population rises
rapidly with the first few reuses of a needle; the
number of estimated cases of injection-associated
HBV is only marginally higher when each needle is
reused nine times compared to four times (14). Our
model does not include such a variable, instead we
simply introduced P(u) as the probability that an
injection is unsafe, and considered each injection
individually. This allowed us to make our final
estimates based on the proportion of injections that
are unsafe, a parameter that we can support with data
from the literature review (16).
The model we have described here is a massaction model, which assumes that everyone in a
population is put at equal risk from unsafe injections.
In fact, there are high-risk and low-risk groups
depending on a number of factors. The prevalence of
pathogens, the susceptibility to infection and the
number of injections received vary considerably by
country, by region, and by age group. More realistic
models would therefore require stratification and
data on all these parameters.
Some other considerations are too complex to
be included in our simple mass-action model, but are
important in any realistic understanding of the risk of
unsafe injections for infants and children. Infants in
developing countries normally receive approximately
five immunization injections in the first year of life, in
addition to any curative injections. Although immunization injections are considered safer in general
than curative injections, the high number of injections received by this susceptible group merits
concern. Many infants acquire HIV and HBV via
the maternal route, and may be highly infectious. HIV
is transmitted to more than one-third of infants of
infected mothers, and HIV-infected infants have
very high blood titres of the virus, presumably
Bulletin of the World Health Organization, 1999, 77 (10)
Transmission of HBV, HCV, and HIV through unsafe injections
resulting in higher infectivity of their blood. For
hepatitis B, the outcome of the disease differs
depending on the age of acquisition; children under
5 years of age have a relatively high chance of
becoming chronic carriers and subsequently developing liver disease, while children over 5 years and
adults have a relatively low chance. A further
consideration is that infants and children with certain
diseases tend to be over-represented in hospitals and
clinics, and therefore the prevalence of infected
blood in contaminated injection equipment may be
higher than the background population prevalence.
One study found that 50% of children in a ward in
sub-Saharan Africa were HIV positive (26).
There are many reasons why unsafe injections
are given in developing countries, the main logistic
reasons being as follows: lack of sufficient quantities
of syringes and needles; lack of operational sterilization equipment or fuel to operate such equipment;
and high patient demand for injections. In many
regions, there is also a lack of understanding on many
levels in the health sector Ð by administrators, health
workers and patients Ð of the real risk of unsafe
injections, or even of what comprises an unsafe
injection. A common misconception is that it is safe
to reuse the syringe between patients if the needle is
changed.
The transmission of hepatitis B, hepatitis C,
and HIV are by no means the only risks involved in
unsafe injections; besides abscesses caused by
bacterial contamination, many outbreaks involving
other pathogens have been linked to unsafe
injections (16). Further investigation of the prevalence of unsafe injection practices, the contribution of unsafe injections to the transmission of
hepatitis viruses and HIV in specific areas, the
reasons for the lack of adequate sterilization
practices, and the feasibility of various strategies
for improving injection safety are urgently needed.
Although the extent of unsafe injection practices is
still poorly documented in many regions (e.g. Latin
America), this model provides an estimate of the
incidence of infection with bloodborne pathogens
that may be expected from various estimated
proportions of unsafe injections. n
Fig. 1. Sensitivity analysis varying proportion of unsafe injections
for 1 or 2 injections per person per year: a) No. of viral hepatitis B
infections per year in India. b) No. of viral hepatitis C infections
per year in other Asian and Pacific islands. c) No. of human
immunodeficiency virus infections per year in sub-Saharan Africa
Acknowledgements
We thank R. Chen, Y. Hutin, A. Battersby and P. van
Damme for their careful review and valuable
comments on the manuscript.
Bulletin of the World Health Organization, 1999, 77 (10)
805
In Focus
ReÂsumeÂ
Transmission du VHB, du VHC et du VIH par des injections pratiqueÂes dans de mauvaises
conditions d'hygieÁne
Des milliards d'injections sont administreÂes chaque
anneÂe dans les pays en deÂveloppement, souvent dans de
mauvaises conditions d'hygieÁne, et la transmission par le
sang de certains agents pathogeÁnes apparaõÃt comme un
probleÁme de sante publique majeur. Nous publions dans
cet article le nombre estimatif, pour le monde et les
reÂgions, des infections par le virus de l'heÂpatite B (VHB),
par le virus de l'heÂpatite C (VHC) et par le virus de
l'immunodeÂficience humaine (VIH) pouvant eÃtre imputeÂes aÁ des injections pratiqueÂes dans de mauvaises
conditions d'hygieÁne dans les pays en deÂveloppement. Le
calcul de ces estimations repose sur des donneÂes
quantitatives relatives aux injections faites dans de
mauvaises conditions d'hygieÁne, aÁ l'efficacite de la
transmission et aÁ la charge de morbidite due au VHB, au
VHC et au VIH, et sur la preÂvalence de l'utilisation
d'injections telle qu'elle ressort d'un examen de la
documentation sur ce domaine.
On a utilise un modeÁle « mass-action » simple
consistant en une eÂquation lineÂaire geÂneÂraliseÂe dont les
variables rendent compte de la preÂvalence d'un germe
pathogeÁne dans une population, de la sensibilite d'une
population, de l'efficacite de la transmission du germe
pathogeÁne, de la proportion d'injections dangereuses et
du nombre d'injections recËues. Le modeÁle a eÂte appliqueÂ
aux donneÂes de recensement mondiales pour obtenir des
estimations prudentes de l'incidence de la transmission.
Le modeÁle fait apparaõÃtre que les injections
pratiqueÂes dans de mauvaises conditions d'hygieÁne
pourraient eÃtre responsables chaque anneÂe d'environ
8±16 millions d'infections dues au VHB, 2±4,5 millions
d'infections dues au VHC et 75 000±150 000 infections
aÁ VIH. La fourchette estimative des infections dues au
VHB correspondait aux estimations comparables baseÂes
sur plusieurs eÂtudes du programme eÂlargi de vaccination
fondeÂes sur la population qui attribuent au moins 20%
des nouvelles infections dues au VHB aÁ des injections
pratiqueÂes dans de mauvaises conditions d'hygieÁne.
Il ressort des reÂsultats obtenus que les injections
pratiqueÂes dans de mauvaises conditions d'hygieÁne
peuvent entraõÃner un grand nombre d'infections dues aÁ
des germes pathogeÁnes transmis par voie sanguine. Une
initiative majeure s'impose donc pour ameÂliorer la
seÂcurite des injections et reÂduire l'utilisation excessive
d'injections dans de nombreux pays.
Resumen
TransmisioÂn del VHB, el VHC y el VIH a traveÂs de inyecciones peligrosas
En los paõÂses en desarrollo se administran cada anÄo miles
de millones de inyecciones, muchas de ellas peligrosas, y
se considera que la propagacioÂn de ciertos agentes
patoÂgenos de transmisioÂn hematoÂgena por esa võÂa
constituye un importante problema de salud puÂblica. En
este artõÂculo presentamos estimaciones mundiales y
regionales del nuÂmero de infecciones por los virus de la
hepatitis B (VHB), la hepatitis C (VHC) y la inmunodeficiencia humana (VIH) atribuibles a inyecciones peligrosas en el mundo en desarrollo. Las estimaciones se
efectuaron empleando datos cuantitativos sobre las
praÂcticas peligrosas de inyeccioÂn, la eficiencia de la
transmisioÂn y la carga de morbilidad por el VHB, el VHC y
el VIH, y la prevalencia del uso de inyecciones
determinada mediante una revisioÂn de la literatura.
Se utilizo un modelo simple de accioÂn de masas
consistente en una ecuacioÂn lineal generalizada con
variables que reflejaban la prevalencia de un agente
patoÂgeno en la poblacioÂn, la susceptibilidad de eÂsta, la
eficiencia de transmisioÂn del agente patoÂgeno, la
806
proporcioÂn de inyecciones peligrosas y el nuÂmero de
inyecciones recibidas. El modelo se aplico a datos
censales mundiales, para obtener estimaciones prudentes de la incidencia de transmisioÂn.
El modelo indica que las inyecciones peligrosas
pueden estar provocando cada anÄo aproximadamente
8-16 millones de infecciones por el VHB, 2±4,5 millones
por el VHC, y 75 000±150 000 por el VIH. El intervalo
estimado para la hepatitis B coincide con estimaciones
similares de varios estudios poblacionales del Programa
Ampliado de InmunizacioÂn, que atribuyen al menos un
20% de las nuevas infecciones por el VHB a las
inyecciones peligrosas.
Los resultados obtenidos indican que las inyecciones peligrosas pueden dar lugar a un elevado nuÂmero
de infecciones por agentes patoÂgenos de transmisioÂn
hematoÂgena. Se necesita por tanto una iniciativa de gran
calibre para mejorar la seguridad de las inyecciones y
reducir el abuso de las mismas en muchos paõÂses.
Bulletin of the World Health Organization, 1999, 77 (10)
Transmission of HBV, HCV, and HIV through unsafe injections
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